反应详情

Thionyl chloride (2.2 mL, 30 mmol) was added to a stirred solution of 2-amino-6-methylbenzoic acid (1.51 g, 10 mmol) in benzene (50 mL) and the mixture was heated at reflux for 18 h. Once cooled, the solvent was removed in vacuo and stripped down twice with benzene (25 mL). The residue was dissolved in CHCl3 (50 mL) and treated with o-toluidine (2.13 mL, 20 mmol). The slurry was then heated at reflux for 3 h. At that time TLC (50% EtOAc/hexane) indicated that the reaction was complete. After cooling to room temperature, the reaction mixture was poured atop a 4 cm plug of silica gel and flushed through with 20% EtOAc/hexane. The product containing fractions were combined and concentrated in vacuo. The residue was dissolved in HOAc (50 mL) and treated with chloroactyl chloride (1.6 mL, 20 mmol) and the mixture was heated at reflux for 18 h. The reaction was cooled and concentrated in vacuo. The remaining HOAc was removed by azeotroping with toluene (25 mL) three times. The residue was dissolved in toluene (10 mL) and poured through a 4 cm plug of silica gel, flushing through with 20% EtOAc/hexane. The product containing fractions were identified by LCMS [MS (ES): m/z 299 (M+)), and concentrated in vacuo to afford 476 mg (16%) as a white foam. The white foam chloride (470 mg, 1.57 mmol) was dissolved in DMF (10 mL) and treated with adenine (423 mg, 3.14 mmol) and K2CO3 (433 mg, 3.14 mmol) and the mixture was stirred overnight at room temperature. The suspension was then poured into 200 mL of H2O, stirred at room temperature for 30 min then chilled in the refrigerator for 30 min. The resultant solid was collected by vacuum filtration and recrystallized from EtOH to afford 123 mg (20%) of an off white solid. mp 281.5-282.7° C. (decomposes). 1H NMR (DMSO-d6) δ: 8.07 (s, 1H); 8.05 (s, 1H); 7.61 (t, J=7.8 Hz, 1H), 7.48 (m, 4H), 7.25 (m, 3H), 5.09 (d, J=17.4 Hz, 1H), 4.76 (d, J=17.4 Hz, 1H), 2.73 (s, 3H), 2.18 (s, 3H). 13C NMR (DMSO-d6) ppm: 161.3, 156.2, 152.8, 151.4, 150.0, 148.5, 142.2, 140.9, 136.1, 135.4, 134.3, 131.7, 130.1, 130.0, 129.0, 128.0, 125.8, 119.2, 118.5, 44.8, 22.9, 17.4. MS (ES): m/z 398.2 (M+). Anal. calcd. for C22H19N7O: C, 66.49; H, 4.82; N, 24.67. Found: C, 66.29; H, 4.78; N, 24.72.

1. temperaturethe mixture was heated
2. temperatureat reflux for 18 h
3. temperatureOnce cooled
4. customthe solvent was removed in vacuo
5. dissolutionThe residue was dissolved in CHCl3 (50 mL)
6. temperatureThe slurry was then heated
7. temperatureat reflux for 3 h
8. additionthe reaction mixture was poured atop a 4 cm plug of silica gel
9. customflushed through with 20% EtOAc/hexane
10. additionThe product containing fractions
11. concentrationconcentrated in vacuo
12. dissolutionThe residue was dissolved in HOAc (50 mL)
13. temperaturethe mixture was heated
14. temperatureat reflux for 18 h
15. temperatureThe reaction was cooled
16. concentrationconcentrated in vacuo
17. customThe remaining HOAc was removed
18. customby azeotroping with toluene (25 mL) three times
19. dissolutionThe residue was dissolved in toluene (10 mL)
20. additionpoured through a 4 cm plug of silica gel
21. customflushing through with 20% EtOAc/hexane
22. additionThe product containing fractions
23. concentrationm/z 299 (M+)), and concentrated in vacuo
24. customto afford 476 mg (16%) as a white foam
25. stirringstirred at room temperature for 30 min
26. temperaturethen chilled in the refrigerator for 30 min
27. filtrationThe resultant solid was collected by vacuum filtration
28. customrecrystallized from EtOH
29. customto afford 123 mg (20%) of an off white solid